Project Summary A recent report has documented the clinical impact of methicillin-resistant Staphylococcus aureus (MRSA), suggesting that MRSA caused over 94,000 serious infections and more than 18,000 deaths in the U.S. in 2005. In the past decade, new groups at risk of acquiring MRSA have emerged, and reports from Europe and Canada have identified another emergent risk group: individuals in contact with live swine. Pilot studies in the U.S. carried out by our group have shown that almost half of the swine workers examined were colonized with MRSA. Though livestock-associated MRSA (LA-MRSA) have been found in an increasing number of countries, most studies have examined a small number of workers using a cross- sectional design conducted on the farm site. A large cohort study of livestock-exposed workers has not been conducted in the U.S., but as the epidemiology of MRSA is rapidly changing, there is a critical need to better understand the epidemiology of novel S. aureus isolates associated with farming exposures. Such knowledge would be invaluable in assessing infectious disease risks and determining preventative measures. Our long-term goal is to better understand the epidemiology of S. aureus in the rural community, including S. aureus collected both inside and outside of the healthcare setting. Our objective in this application is to characterize the epidemiology of S. aureus in a rural state. We will achieve this goal by carrying out two parallel prospective cohort studies, examining 1) individuals enrolled in the Agricultural Health Study, focusing on those who raise swine; 2) a population-based group representing a cross-section of Iowans. While these cohort studies will focus on colonization, we will carry out a third arm examining S.aureus isolates from symptomatic infections in the state. Our central hypothesis is that individuals working with livestock will be at risk of occupational exposure to MRSA, and that livestock-associated strains will also be causing symptomatic infections. Our rationale for this project is that successful completion will allow for the development of interventions targeting emerging S. aureus strains prior to their widespread dissemination in the human population. The proposed research is innovative because it is designed to prospectively examine the epidemiology of S. aureus in an agricultural/rural setting, which represents 40% of the community hospitals in the U.S. At the completion of this research, it is our expectation that we will have established the prevalence and dominant molecular types of S. aureus in rural Iowans; delineated risk factors for colonization with antibiotic-resistant S. aureus strains, and the frequency with which these cause symptomatic infection in our cohorts; and determined the molecular epidemiology of MRSA strains causing symptomatic infections in Iowa. These results will provide insight into the maintenance and spread of S. aureus in the rural environment, as well as potential mechanisms that could be implemented to prevent such emergence and spread.